Noninvasive diagnosis of BK virus nephritis by measurement of messenger RNA for BK virus VP1 in urine

Ruchuang Ding, Mara Medeiros, Darshana Dadhania, Thangamani Muthukumar, David Kracker, Jin M. Kong, Susanna R. Epstein, Vijay K. Sharma, Surya V. Seshan, Baogui Li, Manikkam Suthanthiran

Research output: Contribution to journalArticle

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Abstract

Background. Polyoma virus type BK (BKV) nephritis has emerged as an important cause of renal allograft dysfunction and graft failure. Its diagnosis is contingent on the invasive procedure of allograft biopsy. A noninvasive diagnostic test for BKV nephritis could improve clinical outcome. Methods. We obtained 25 urine specimens from 8 renal allograft recipients with biopsy-confirmed BKV nephritis, 31 samples from 28 recipients in whom BKV nephritis was excluded by allograft biopsy, and 74 specimens from 34 patients with stable allograft function. RNA was isolated from the urinary cells and reverse transcribed to complementary DNA. We designed gene-specific oligonucleotide primers and probes for the measurement of messenger RNA (mRNA) encoding BKV VP1 protein and a constitutively expressed 18S ribosomal RNA (rRNA) by real-time quantitative polymerase chain reaction. We explored the hypothesis that BKV VP1 mRNA levels predict BKV nephritis. Results. The levels of BKV VP1 mRNA but not the levels of 18S rRNA predicted BKV nephritis. Analysis involving the receiver operating characteristic curve demonstrated that BKV nephritis can be predicted with a sensitivity of 93.8% and a specificity of 93.9% with the use of a cutoff value of 6.5x105 BKV VP1 mRNA copy number per nanogram of total RNA (P<0.00001). In the receiver operating characteristic curve analysis, the calculated area under the curve was 0.949 (95% confidence interval, 0.912 to 0.987, P<0.00001) for BKV VP1 mRNA levels and 0.562 (95% confidence interval, 0.417 to 0.708, P>0.2) for 18S rRNA. Conclusions. Measurement BKV VP1 mRNA in urinary cells offers a noninvasive and accurate means of diagnosing BKV nephritis.

Original languageEnglish
Pages (from-to)987-994
Number of pages8
JournalTransplantation
Volume74
Issue number7
Publication statusPublished - 15 Oct 2002
Externally publishedYes

Fingerprint

BK Virus
Nephritis
Urine
Allografts
18S Ribosomal RNA
Messenger RNA
Biopsy
Kidney
Polyomavirus
DNA Primers
Oligonucleotide Probes
Routine Diagnostic Tests
ROC Curve
Real-Time Polymerase Chain Reaction
Complementary DNA
Transplants

ASJC Scopus subject areas

  • Transplantation

Cite this

Ding, R., Medeiros, M., Dadhania, D., Muthukumar, T., Kracker, D., Kong, J. M., ... Suthanthiran, M. (2002). Noninvasive diagnosis of BK virus nephritis by measurement of messenger RNA for BK virus VP1 in urine. Transplantation, 74(7), 987-994.

Noninvasive diagnosis of BK virus nephritis by measurement of messenger RNA for BK virus VP1 in urine. / Ding, Ruchuang; Medeiros, Mara; Dadhania, Darshana; Muthukumar, Thangamani; Kracker, David; Kong, Jin M.; Epstein, Susanna R.; Sharma, Vijay K.; Seshan, Surya V.; Li, Baogui; Suthanthiran, Manikkam.

In: Transplantation, Vol. 74, No. 7, 15.10.2002, p. 987-994.

Research output: Contribution to journalArticle

Ding, R, Medeiros, M, Dadhania, D, Muthukumar, T, Kracker, D, Kong, JM, Epstein, SR, Sharma, VK, Seshan, SV, Li, B & Suthanthiran, M 2002, 'Noninvasive diagnosis of BK virus nephritis by measurement of messenger RNA for BK virus VP1 in urine', Transplantation, vol. 74, no. 7, pp. 987-994.
Ding R, Medeiros M, Dadhania D, Muthukumar T, Kracker D, Kong JM et al. Noninvasive diagnosis of BK virus nephritis by measurement of messenger RNA for BK virus VP1 in urine. Transplantation. 2002 Oct 15;74(7):987-994.
Ding, Ruchuang ; Medeiros, Mara ; Dadhania, Darshana ; Muthukumar, Thangamani ; Kracker, David ; Kong, Jin M. ; Epstein, Susanna R. ; Sharma, Vijay K. ; Seshan, Surya V. ; Li, Baogui ; Suthanthiran, Manikkam. / Noninvasive diagnosis of BK virus nephritis by measurement of messenger RNA for BK virus VP1 in urine. In: Transplantation. 2002 ; Vol. 74, No. 7. pp. 987-994.
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abstract = "Background. Polyoma virus type BK (BKV) nephritis has emerged as an important cause of renal allograft dysfunction and graft failure. Its diagnosis is contingent on the invasive procedure of allograft biopsy. A noninvasive diagnostic test for BKV nephritis could improve clinical outcome. Methods. We obtained 25 urine specimens from 8 renal allograft recipients with biopsy-confirmed BKV nephritis, 31 samples from 28 recipients in whom BKV nephritis was excluded by allograft biopsy, and 74 specimens from 34 patients with stable allograft function. RNA was isolated from the urinary cells and reverse transcribed to complementary DNA. We designed gene-specific oligonucleotide primers and probes for the measurement of messenger RNA (mRNA) encoding BKV VP1 protein and a constitutively expressed 18S ribosomal RNA (rRNA) by real-time quantitative polymerase chain reaction. We explored the hypothesis that BKV VP1 mRNA levels predict BKV nephritis. Results. The levels of BKV VP1 mRNA but not the levels of 18S rRNA predicted BKV nephritis. Analysis involving the receiver operating characteristic curve demonstrated that BKV nephritis can be predicted with a sensitivity of 93.8{\%} and a specificity of 93.9{\%} with the use of a cutoff value of 6.5x105 BKV VP1 mRNA copy number per nanogram of total RNA (P<0.00001). In the receiver operating characteristic curve analysis, the calculated area under the curve was 0.949 (95{\%} confidence interval, 0.912 to 0.987, P<0.00001) for BKV VP1 mRNA levels and 0.562 (95{\%} confidence interval, 0.417 to 0.708, P>0.2) for 18S rRNA. Conclusions. Measurement BKV VP1 mRNA in urinary cells offers a noninvasive and accurate means of diagnosing BKV nephritis.",
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AU - Ding, Ruchuang

AU - Medeiros, Mara

AU - Dadhania, Darshana

AU - Muthukumar, Thangamani

AU - Kracker, David

AU - Kong, Jin M.

AU - Epstein, Susanna R.

AU - Sharma, Vijay K.

AU - Seshan, Surya V.

AU - Li, Baogui

AU - Suthanthiran, Manikkam

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Y1 - 2002/10/15

N2 - Background. Polyoma virus type BK (BKV) nephritis has emerged as an important cause of renal allograft dysfunction and graft failure. Its diagnosis is contingent on the invasive procedure of allograft biopsy. A noninvasive diagnostic test for BKV nephritis could improve clinical outcome. Methods. We obtained 25 urine specimens from 8 renal allograft recipients with biopsy-confirmed BKV nephritis, 31 samples from 28 recipients in whom BKV nephritis was excluded by allograft biopsy, and 74 specimens from 34 patients with stable allograft function. RNA was isolated from the urinary cells and reverse transcribed to complementary DNA. We designed gene-specific oligonucleotide primers and probes for the measurement of messenger RNA (mRNA) encoding BKV VP1 protein and a constitutively expressed 18S ribosomal RNA (rRNA) by real-time quantitative polymerase chain reaction. We explored the hypothesis that BKV VP1 mRNA levels predict BKV nephritis. Results. The levels of BKV VP1 mRNA but not the levels of 18S rRNA predicted BKV nephritis. Analysis involving the receiver operating characteristic curve demonstrated that BKV nephritis can be predicted with a sensitivity of 93.8% and a specificity of 93.9% with the use of a cutoff value of 6.5x105 BKV VP1 mRNA copy number per nanogram of total RNA (P<0.00001). In the receiver operating characteristic curve analysis, the calculated area under the curve was 0.949 (95% confidence interval, 0.912 to 0.987, P<0.00001) for BKV VP1 mRNA levels and 0.562 (95% confidence interval, 0.417 to 0.708, P>0.2) for 18S rRNA. Conclusions. Measurement BKV VP1 mRNA in urinary cells offers a noninvasive and accurate means of diagnosing BKV nephritis.

AB - Background. Polyoma virus type BK (BKV) nephritis has emerged as an important cause of renal allograft dysfunction and graft failure. Its diagnosis is contingent on the invasive procedure of allograft biopsy. A noninvasive diagnostic test for BKV nephritis could improve clinical outcome. Methods. We obtained 25 urine specimens from 8 renal allograft recipients with biopsy-confirmed BKV nephritis, 31 samples from 28 recipients in whom BKV nephritis was excluded by allograft biopsy, and 74 specimens from 34 patients with stable allograft function. RNA was isolated from the urinary cells and reverse transcribed to complementary DNA. We designed gene-specific oligonucleotide primers and probes for the measurement of messenger RNA (mRNA) encoding BKV VP1 protein and a constitutively expressed 18S ribosomal RNA (rRNA) by real-time quantitative polymerase chain reaction. We explored the hypothesis that BKV VP1 mRNA levels predict BKV nephritis. Results. The levels of BKV VP1 mRNA but not the levels of 18S rRNA predicted BKV nephritis. Analysis involving the receiver operating characteristic curve demonstrated that BKV nephritis can be predicted with a sensitivity of 93.8% and a specificity of 93.9% with the use of a cutoff value of 6.5x105 BKV VP1 mRNA copy number per nanogram of total RNA (P<0.00001). In the receiver operating characteristic curve analysis, the calculated area under the curve was 0.949 (95% confidence interval, 0.912 to 0.987, P<0.00001) for BKV VP1 mRNA levels and 0.562 (95% confidence interval, 0.417 to 0.708, P>0.2) for 18S rRNA. Conclusions. Measurement BKV VP1 mRNA in urinary cells offers a noninvasive and accurate means of diagnosing BKV nephritis.

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